Engineering a Targeted Delivery System for Probiotics

Abstract

The clinical and commercial application of probiotics is constrained by challenges related to poor stability during storage and gastrointestinal (GI) transit. Despite the inclusion of large colony-forming unit (CFU) counts in many commercial products, survival through the stomach and functional colonisation of the distal gut remains inconsistent. This thesis aimed to develop a series of core and core-shell structures, with biocompatible properties to enhance the viability, targeted release, improved mucoadhesion, and colon-specific delivery of probiotics.

The encapsulation systems were based on a sodium alginate matrix, selected for its food-grade compatibility and ionotropic gelation properties. The encapsulated probiotics produced using the Buchi B-390 demonstrated high encapsulation efficiency (>95%) and optimal processability. Calcium carbonate (CaCO₃) was incorporated as a dual-function agent—acting both as an internal crosslinker to improve matrix integrity and as a pH buffer to neutralise acidic environments. Using a novel release assay based on fluorescent microbeads, it was shown that calcium carbonate formulations held matrix contents more tightly under acidic conditions.

Lipid-core core–shell microparticles were fabricated by integrating avocado oil structured with hydroxypropyl methylcellulose (HPMC) as a hydrophobic internal phase. These were encased within an alginate–CaCO₃ shell. However, during in vitro digestion the release of the core-shell oil microparticles within gastric acid was 48.1 ± 3.2% and 42.1 ± 2.9% (alginate and alginate + calcium carbonate shell respectively), emphasises the need for better interfacial stabilization or secondary barrier coatings in lipid-based designs.